基本信息:
- 专利标题： IDO INHIBITORS AND THERAPEUTIC USES THEREOF
- 专利标题（中）：IDO抑制剂及其治疗用途
- 申请号：PCT/EP2009/054482 申请日：2009-04-15
- 公开(公告)号：WO2009127669A2 公开(公告)日：2009-10-22
- 发明人： ROEHRIG, Ute , LOAY, Awad , MICHIELIN, Olivier , VAN DEN EYNDE, Benoit , PILOTTE, Luc , STROOBANT, Vincent , LARRIEU, Pierre
- 申请人： LUDWIG INSTITUTE FOR CANCER RESEARCH LTD , ROEHRIG, Ute , LOAY, Awad , MICHIELIN, Olivier , VAN DEN EYNDE, Benoit , PILOTTE, Luc , STROOBANT, Vincent , LARRIEU, Pierre
- 申请人地址： 605 Third Avenue New York, New York 10158 US
- 专利权人： LUDWIG INSTITUTE FOR CANCER RESEARCH LTD,ROEHRIG, Ute,LOAY, Awad,MICHIELIN, Olivier,VAN DEN EYNDE, Benoit,PILOTTE, Luc,STROOBANT, Vincent,LARRIEU, Pierre
- 当前专利权人： LUDWIG INSTITUTE FOR CANCER RESEARCH LTD,ROEHRIG, Ute,LOAY, Awad,MICHIELIN, Olivier,VAN DEN EYNDE, Benoit,PILOTTE, Luc,STROOBANT, Vincent,LARRIEU, Pierre
- 当前专利权人地址： 605 Third Avenue New York, New York 10158 US
- 代理机构： WRIGHT, Robert Gordon McRae
- 优先权： GB0806794.4 20080415
- 主分类号： A61K31/05
- IPC分类号： A61K31/05 ; A61K31/085 ; A61K31/12 ; A61K31/136 ; A61K31/167 ; A61K31/4045
摘要：
Compounds of formula (I), and pharmaceutically acceptable salts thereof, in which each compound is adapted to occupy the binding site of human IDO, which comprises a large hydrophobic pocket A and a second, proximal hydrophobic pocket B, the compound comprising at least one of the following elements: (i) a large hydrophobic fragment to substantially fill pocket A in the binding site of human IDO; (ii) an atom that can coordinate to the heme iron of human IDO, (iii) a positively charged group that can form a salt-bridge with the heme 7-propionate of the human IDO; (iv) a negatively charged group that can form a salt-bridge with Arg231 of the human IDO; (v) a hydrophobic group that can form van der Waals interactions with pocket B; and (vi) one or more substituents that can hydrogen bond to Serl67 and to Gly262, and as IDO inhibitors and their therapeutic use, eg in the treatment of cancer.
摘要（中）：
其中每种化合物适于占据人IDO的结合位点的式（I）化合物及其药学上可接受的盐，其包含大的疏水性口袋A和第二近端疏水口袋B，所述化合物包含至少一种 的以下元素：（i）大的疏水性片段，以基本上填充人IDO的结合位点中的口袋A; （ii）可以配合人类IDO的血红素铁的原子，（iii）可以与人类IDO的7-丙酸血红素形成盐桥的带正电荷的基团; （iv）可以与人类IDO的Arg231形成盐桥的带负电荷的基团; （v）可与袋B形成范德华相互作用的疏水基团; 和（vi）一个或多个可以与Ser1667氢键连和Gly262的取代基，以及作为IDO抑制剂及其治疗用途，例如用于治疗癌症。
IPC结构图谱:
| A | 人类生活必需 |
| --A61 | 医学或兽医学；卫生学 |
| ----A61K | 医用、牙科用或梳妆用的配制品 |
| ------A61K31/00 | 含有机有效成分的医药配制品 |
| --------A61K31/045 | .羟基化合物，例如醇类；其盐类，例如醇化物 |
| ----------A61K31/05 | ..酚类 |